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AimAdverse (poor or excessive) fetal growth “programs” an elevated risk of type 2 diabetes. Fatty acid binding protein 4 (FABP4) has been implicated in regulating insulin sensitivity and lipid metabolism relevant to fetal growth. We sought to determine whether FABP4 is associated with poor or excessive fetal growth and fetal lipids.MethodsIn a nested case-control study in the Shanghai Birth Cohort including 60 trios of small-for-gestational-age (SGA, an indicator of poor fetal growth), large-for-gestational-age (LGA, an indicator of excessive fetal growth) and optimal-for-gestational-age (OGA, control) infants, we measured cord blood concentrations of FABP4 and lipids [high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterols, triglycerides (TG)].ResultsAdjusting for maternal and neonatal characteristics, higher cord blood FABP4 concentrations were associated with a lower odds of SGA [OR = 0.29 (0.11–0.77) per log unit increment in FABP4, P = 0.01], but were not associated with LGA (P = 0.46). Cord blood FABP4 was positively correlated with both LDL (r = 0.29, P = 0.025) and HDL (r = 0.33, P = 0.01) in LGA infants only.ConclusionFABP4 was inversely associated with the risk of SGA. The study is the first to demonstrate LGA-specific positive correlations of cord blood FABP4 with HDL and LDL cholesterols, suggesting a role of FABP4 in fetal lipid metabolism in subjects with excessive fetal growth.

In this paper, the simulated welding structure at different areas of heat affected zone (HAZ) of austenitic stainless steel are prepared by heating furnace, and the deference of intergranular corrosion resistance of all samples were determined by comparative methods of oxalic acid etching, hot-acid test and electrochemical potentiodynamic reactivation tests (EPR), and the effectiveness of all those methods were analysis and determination at the same time. The result shows that the susceptibility degree at different areas of HAZ increased with the heating temperature increase, but all structures can pass hot-acid test and EPR test, indicating that it could maintain good performance of intergranular corrosion resistance. The hot-acid test results have good consistency with EPR test , but inconsistent with oxalic acid etching test. The results show that the evaluation of oxalic acid etching is too much strict to be used as a judgment method, so that not suitable of use for inspection.

In this paper, the simulated welding structure in different area of heat affected zone (HAZ) of S30408 austenitic stainless steel are prepared, and the corrosion resistance properties are evaluated by electrochemistry method and micro-morphology analysis. The result shows that the corrosion resistance of different areas of the HAZ presents different performance, and the corrosion resistance of the area with the highest heating temperature of 1000-1100 °C is slightly lower than that of other areas.The micro-morphology shows that the pitting of the simulated structure in the HAZ have a certain orientation. The rapid cooling process at high temperature is conducive to the uniform distribution of alloying elements, and it can increase the pitting corrosion resistance of the raw material.

Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.

Methyl jasmonate (MeJA) has been widely used to improve the biosynthesis of secondary metabolites such as triterpenoid saponins in medicinal plants. However, the underlying molecular mechanisms remain poorly understood. Differing from roots that accumulate protopanaxatriol-type saponins, Panax notoginseng leaves with a lower biomass mainly contain protopanaxadiol (PPD)-type saponins. Therefore, it is interesting to explore whether MeJA can activate the biosynthesis of PPD-type saponins in P. notoginseng leaves. In this study, we found MeJA could effectively induce the accumulation of PPD-type saponins, including ginsenoside Rb1, Rc, Rb2, Rb3 and notoginsenoside Fa, Fe in P. notoginseng leaves based on a newly established high-performance liquid chromatography method. Transcriptome analysis showed that differentially expressed genes (DEGs) induced by MeJA were mainly enriched in “terpenoid backbone biosynthesis”, “biosynthesis of unsaturated fatty acids”, “sesquiterpenoid and triterpenoid biosynthesis”, “fatty acid metabolism”, and “phenylpropanoid biosynthesis”. Furthermore, the expression profile and quantitative real-time PCR analysis of DEGs showed that MeJA could positively induce the molecular response of endogenous jasmonic acid (JA) signaling pathway, and increased PPD-type saponins mediated by MeJA in P. notoginseng leaves may be related to the high expression of FPS, SS, SE, DS and UGTs, and the low expression of CYP716A53v2 and β-AS. The results provide a molecular understanding for MeJA-elicited biosynthesis of triterpenoid saponins and facilitate the further characterization of the genes responsible for biosynthesis of PPD-type saponins in P. notoginseng leaves.

Flavonoids are rich in tea plants (Camellia sinensis), and responsible for the flavor and healthful benefits of tea beverage. The anthocyanin levels in the purple tender shoots are higher than in the general green leaves of tea plant, which provide special materials to search metabolic mechanisms of flavonoid enrichment in plant. In this work, flavonoid differences between purple and green shoots from tea cultivars “Zijuan” (ZJ) and “Yunkang10” (YK-10) were investigated through metabolomic analysis, and mechanisms for their difference were surveyed by comparative transcriptomic and proteomic analysis. Levels of 34 flavonoids were different between ZJ and YK-10 shoots. Among them, 8 and 6 were marker metabolites in ZJ and YK-10, respectively. The differentially expressed genes (DEGs), differentially expressed proteins (DEPs), and different-level metabolites (DLMs) between ZJ and YK-10 were researched, respectively; and interactions including DEG-DLM, DEP-DLM, DEG-DEP, and DEG-DEP-DLM were analyzed; the contents of 18 characteristic flavonoids in tea leaves and expressions of 34 flavonoid metabolic genes were measured to verify the omics results. Integrated above analyses, a proposed model of flavonoids biosynthesis in tea shoots were established. The differential expression of the leucoanthocyanidin reductase (LAR), anthocyanidin synthase (ANS), anthocyanidin reductase (ANR), UDPG-flavonoid glucosyltransferase (UGT) 75L12 and 94P1 at gene level, and the ANS, ANR, and UGT78A15 at protein level, were closely associated with differences in flavonoids between ZJ and YK-10 shoot. Together, this study provides new information on the flavonoid accumulation mechanism in tea plant.

Yuanli Huang,1,2 Guanghui Zhang,1,2 Qing Zhu,1 Xia Wu,3 Ligao Wu1 1Department of Pathology, the First Affiliated Hospital of Bengbu Medical College, Bengbu City, Anhui Province, People’s Republic of China; 2Graduate School of Bengbu Medical College, Bengbu City, Anhui Province, People’s Republic of China; 3Department of Pathology, Fuyang Tumor Hospital, Fuyang City, Anhui Province, People’s Republic of ChinaCorrespondence: Ligao Wu Tel +86 15395225588Email wlgahbb@126.comPurpose: Pyroptosis is a recently discovered highly inflammatory form of programmed cell death, during which the N-terminus of the cleaved Gasdermin protein family forms pores in the cell membrane, leading to cell disintegration and the release of certain intracellular factors, including caspase3, gasdermin E (GSDME), and high mobility group proteins (HMGB1), which trigger a series of secondary inflammatory reactions. Specifically, caspase3 can lyse GSDME and induce pyrolysis, while HMGB1 is released passively after cell membrane destruction. In this study, the roles of these proteins in lung cancer tissues as well as their clinical significance were investigated.Patients and Methods: The expression levels of GSDME, caspase3, and HMGB1 proteins in lung cancer and paracancerous tissues were determined via immunohistochemical staining, and their relationship with the clinical stage, pathological grade, and survival prognosis of the patients was analyzed. Further, CD8+ T cell accumulation in the above-mentioned tissues was also determined, and differences between them with respect to CD8+T cell distribution were also investigated. Furthermore, the relationships between CD8+ T cell abundance and the expression levels of the above-mentioned proteins were determined via statistical analyses.Results: Lung cancer and paracancerous tissues showed significantly different GSDME, caspase3, and HMGB1 protein expression levels. GSDME expression level and the presence or absence of lymph node invasion were identified as prognostic indicators of survival in patients with lung cancer. Surprisingly, however, HMGB1, which showed a certain level of correlation with the presence or absence of lymph node metastasis, could not be used as a prognostic indicator of survival.Conclusion: GSDME may be an important prognostic indicator of survival in patients with lung cancer. However, the effects of HMGB1 expression level and CD8+ T cell abundance on the prognosis of patients with lung cancer still need further investigation.Keywords: cell pyroptosis, caspase3, GSDME, HMGB1, lung cancer, CD8+T

Cucurbitacin IIa is a triterpene isolated exclusively from Hemsleya plants, which is non-steroidal anti-inflammatory drug that function as the main ingredient of Hemslecin capsules and Supplemental Tablets in China. In this study, the biosynthetic pathway of cucurbitacin IIa was elucidated by characterization of squalene epoxidases (HcSE1, HcSE2), cucurbitenol synthases (HcOSC6) and acyltransferases (HcAT1) in Hemsleya chinensis. Meanwhile, cycloartenol synthases (HcOSC1), isomultiflorenol synthases (HcOSC5) and β-amyrin synthase (HcOSC2-4) involved in sterol and triterpenes biosynthesis were functionally illustrated. The high-level production of yeast the key cucurbitacin precursor, cucurbitadienol, was constructed to produce 296.37 mg/L cucurbitadienol and 722.99 mg/L total triterpenoid which is the highest yield cucurbitadienol from known engineered microbes. Moreover, production of cucurbitenol in transient expression of tobacco was employed to achieve 94.8 mg/g dry weight (dw) cucurbitenol from leaves. In this study, the key genes involved in cucurbitacin IIa biosynthesis were identified to facilitate its medical applications via biosynthetic strategy. Meanwhile, the high-level production of cucurbitadienol chassis yeast and tobacco transient expression offered a robust and sSupplemental Table substrate for pharmaceutical cucurbitacin production and screening platform for candidate genes involved in cucurbitacin biosynthesis.

Siberian ginseng (Eleutherococcus senticosus, also known as ciwujia) belongs to the Araliaceae family, which contains more than 1,500 species in 41 genera with diverse chromosome numbers and genome sizes. General consensus posits that ancient whole-genome duplication events and rapid evolutionary radiation are the driving forces for this variation in genome properties. In an attempt to generate more genomic information for the Araliaceae family, we report a 1.30 Gb high-quality draft genome assembly (contig N50 = 309.43 kb) of E. senticosus via PacBio long reads and Hi-C chromatin interaction maps. We found that transposable elements accounted for 72.82% of the genome and a total of 36,372 protein-coding genes were predicted. Comparative analyses of the E. senticosus, Panax notoginseng and Daucus carota genomes revealed a burst expansion of Tekay chromoviral elements in Araliaceae after its divergence with Apiaceae. We also found that E. senticosus underwent a lineage-specific whole-genome duplication event Es-α and a whole-genome duplication event Araliaceae-β that was probably shared by all Araliaceae species. Even though the rediploidization of the E. senticosus genome is evident, pathway analyses show that these two whole-genome duplication events may have contributed to the adaptation of E. senticosus to a cold environment. Taken together, the high-quality genome assembly of E. senticosus provides a valuable genomic resource for future research on the evolution of Araliaceae.

OBJECTIVE To determine the effect of mitochondrial DNA copy number (mtDNAcn) as a biomarker of benzene exposure. METHODS A total of 294 benzene-exposed workers and 102 controls were recruited. Biomarkers of mtDNAcn, cytokinesis-block micronucleus (MN) frequency, and peripheral blood white blood cells (WBC) were detected. Eighteen polymorphism sites in DNA damage repair and metabolic genes were analyzed. RESULTS Benzene exposure increased mtDNAcn and indicated a dose-response relationship (P

Pinocembrin derived flavones are the major bioactive compounds presented in the Lamiaceae plants that have long been of interest due to their great pharmaceutical and economical significance. Modifications on the central skeleton of the flavone moiety have a huge impact on their biological activities. However, the enzymes responsible for structure modification of most flavones are either inefficient or remain unidentified. By integrating omics analysis of Scutellaria barbata and synthetic biology tools in yeast chassis, we characterized a novel gene encoding flavone 7-O-methyltransferase (F7OMT) and discovered a new flavone 8-hydroxylase (F8H) with increased activity. We also identified a series of flavone 6-hydroxylases (F6Hs) and flavone 8-O-methyltransferases (F8OMTs) in this study. Subsequently, we constructed the biosynthetic pathway for chrysin production by assembling catalytic elements from different species and improved the titer to 10.06 mg/L. Using the established chrysin production platform, we achieved the de novo biosynthesis of baicalein, baicalin, norwogonin, wogonin, isowogonin, and moslosooflavone in yeast. Our results indicated that the combination of omics and synthetic biology can greatly speed up the efficiency of gene mining in plants and the engineered yeasts established an alternative way for the production of pinocembrin derivatives.

Erigeron breviscapus is an important medicinal plant in Compositae and the first species to realize the whole process from the decoding of the draft genome sequence to scutellarin biosynthesis in yeast. However, the previous low‐quality genome assembly has hindered the optimization of candidate genes involved in scutellarin synthesis and the development of molecular‐assisted breeding based on the genome. Here, the E. breviscapus genome was updated using PacBio RSII sequencing data and Hi‐C data, and increased in size from 1.2 Gb to 1.43 Gb, with a scaffold N50 of 156.82 Mb and contig N50 of 140.95 kb, and a total of 43,514 protein‐coding genes were obtained and oriented onto nine pseudo‐chromosomes, thus becoming the third plant species assembled to chromosome level after sunflower and lettuce in Compositae. Fourteen genes with evidence for positive selection were identified and found to be related to leaf morphology, flowering and secondary metabolism. The number of genes in some gene families involved in flavonoid biosynthesis in E. breviscapus have been significantly expanded. In particular, additional candidate genes involved in scutellarin biosynthesis, such as flavonoid‐7‐O‐glucuronosyltransferase genes (F7GATs) were identified using updated genome. In addition, three candidate genes encoding indole‐3‐pyruvate monooxygenase YUCCA2 (YUC2), serine carboxypeptidase‐like 18 (SCPL18), and F‐box protein (FBP), respectively, were identified to be probably related to leaf development and flowering by resequencing 99 individuals. These results provided a substantial genetic basis for improving agronomic and quality traits of E. breviscapus, and provided a platform for improving other draft genome assemblies to chromosome‐level.

Although perovskite light-emitting diodes (PeLEDs) are promising for next-generation displays and lighting, their efficiency is still considerably below that of conventional inorganic and organic counterparts. Significant efforts in various aspects of the electroluminescence process are required to achieve high-performance PeLEDs. Here, we present an improved flexible PeLED structure based on the rational interface engineering for energy-efficient photon generation and enhanced light outcoupling. The interface-stimulated crystallization and defect passivation of the perovskite emitter are synergistically realized by tuning the underlying interlayer, leading to the suppression of trap-mediated nonradiative recombination losses. Besides approaching highly emissive perovskite layers, the outcoupling of trapped light is also enhanced by combining the silver nanowires-based electrode with quasi-random nanopatterns on flexible plastic substrate. Upon the collective optimization of the device structure, a record external quantum efficiency of 24.5% is achieved for flexible PeLEDs based on green-emitting CsPbBr3 perovskite.

White organic light-emitting diodes (WOLEDs) using thermally activated delayed fluorescence (TADF)-based single emissive layer (SEL) have attracted enormous attention because of their simple device structure and full exciton utilization potential for high efficiency. However, WOLEDs made of an all-TADF SEL usually exhibit serious efficiency roll-off and poor color stability due to serious exciton-annihilation and unbalanced radiative decays of different TADF emitters. Herein, a new strategy is proposed to manipulate the TADF-sensitized fluorescence process by combining dual-host systems of high triplet energy with a conventional fluorescent emitter of complementary color. The multiple energy-funneling paths are modulated and short-range Dexter energy transfer is largely suppressed due to the steric effect of peripheral tert-butyl group in the blue TADF sensitizer. The resulting all-fluorescent WOLEDs achieve an unprecedentedly high external quantum efficiency of 21.8% with balanced white emission of Commission Internationale de l'Eclairage coordinate of (0.292, 0.343), accompanied with good color stability, reduced efficiency roll-off, and prolonged operational lifetime. These findings demonstrate the validity of this strategy for precisely allocating the exciton harvesting in SEL WOLEDs.

Fibroblast growth factor 19 (FGF19) has been implicated in glucose homeostasis. Gestational diabetes mellitus (GDM) enhances fetal insulin secretion and fetal growth. Girls weigh less and are more insulin resistant than boys at birth. We sought to assess whether FGF19 is associated with GDM and fetal growth and explore potential sex dimorphic associations. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns of GDM versus euglycemic mothers matched by infant’s sex and gestational age at birth. Cord plasma FGF19, insulin, C-peptide, proinsulin, IGF-I and IGF-II concentrations were measured. Cord plasma FGF19 concentrations were similar in GDM versus euglycemic pregnancies (mean ± SD: 43.5 ± 28.2 versus 44.5 ± 30.2 pg/mL, P=0.38). FGF19 was not correlated with IGF-I or IGF-II. FGF19 concentrations were positively correlated with birth weight (r=0.23, P=0.01) and length (r=0.21, P=0.02) z scores, C-peptide (r=0.27, P=0.002) and proinsulin (r=0.27, P=0.002) concentrations in females. Each SD increment in cord plasma FGF19 was associated with a 0.25 (0.07-0.43) increase in birth weight z score in females. In contrast, FGF19 was not correlated with birth weight or length in males. These sex dimorphic associations remained after adjusting for maternal and neonatal characteristics. The study is the first to demonstrate that GDM does not matter for cord blood FGF19 concentrations. The female specific positive correlation between FGF19 and birth weight is suggestive of a sex-dimorphic role of FGF19 in fetal growth. The observations call for more studies to validate the novel findings and elucidate the underlying mechanisms.

R2 R3-MYB transcription factors are ubiquitous in plants, playing a role in the regulation of plant growth, development, and secondary metabolism. In this paper, the R2 R3-MYB transcription factors were identified by bioinformatics analysis of the genomic data of Erigeron breviscapus, and their gene sequences, structures, physical and chemical properties were analyzed. The functions of R2 R3-MYB transcription factors were predicted by cluster analysis. Meanwhile, the expression patterns of R2 R3-MYB transcription factors in response to hormone treatments were analyzed. A total of 108 R2 R3-MYB transcription factors, named EbMYB1-EbMYB108, were identified from the genome of E. breviscapus. Most of the R2 R3-MYB genes carried 2-4 exons. The phylogenetic tree of MYBs in E. breviscapus and Arabidopsis thaliala was constructed, which classified 234 MYBs into 30 subfamilies. The MYBs in the five MYB subfamilies of A.thaliala were clustered into independent clades, and those in E. breviscapus were clustered into four clades. The transcriptome data showed that MYB genes were differentially expressed in different tissues of E. breviscapus and in response to the treatments with exogenous hormones such as ABA, SA, and GA for different time. The transcription of 13 R2 R3-MYB genes did not change significantly, and the expression patterns of some genes were up-regulated or down-regulated with the extension of hormone treatment time. This study provides a theoretical basis for revealing the mechanisms of R2 R3-MYB transcription factors in regulating the growth and development, stress(hormone) response, and active ingredient accumulation in E. breviscapus.

Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.

For the development of solution-processed organic light-emitting diodes (OLEDs), it is highly desirable yet challenging to realize solution-processable non-doped thermally activated delayed fluorescence (TADF) emitters due to their high efficiency and excellent compatibility to the wet methods. Herein, two pairs of blue TADF isomers are designed and synthesized with a hetero-donor configuration for the realization of high photoluminescent quantum yield. The incorporation of two tert-butyl groups in the molecules can effectively increase the molecular solubility and reduce the aggregation-caused self-quenching of excitons in neat films by inhibiting the intramolecular vibrational relaxation and the intermolecular π–π stacking. Solution-processed non-doped OLEDs are achieved with these blue TADF emitters, exhibiting the record-high external quantum efficiencies (EQE) of 25.8%. Furthermore, an all-TADF white OLED with an EQE of 27.3% is also achieved by employing a single emitting layer with the blue TADF emitter as a host for an orange-red TADF dopant.

Retinol-binding protein 4 (RBP-4) is an adipokine involved in regulating insulin sensitivity which would affect fetal growth. It is unclear whether RBP-4 is associated with fetal overgrowth, and unexplored which fetal growth factor(s) may mediate the association. In the Shanghai Birth Cohort, we studied 125 pairs of larger-for-gestational-age (LGA, birth weight >90th percentile, an indicator of fetal overgrowth) and optimal-for-gestational-age (OGA, 25–75th percentiles) control infants matched by sex and gestational age. We measured cord blood concentrations of RBP-4, insulin, proinsulin, insulin-like growth factor-I (IGF-I), and IGF-II. Cord blood RBP-4 concentrations were elevated in LGA vs. OGA infants (21.9 ± 6.2 vs. 20.2 ± 5.1 µg/ml, P = 0.011), and positively correlated with birth weight z score (r = 0.19, P = 0.003), cord blood proinsulin (r = 0.21, P

Panax japonicus var. major is a rare and endangered Chinese traditional medicinal plant that simultaneously forms two types of rhizomes (Swp: Swollen part and Slp: Slender part). However, t...